An open-label randomized clinical trial of prophylactic paracetamol coadministered with 7-valent pneumococcal conjugate vaccine and hexavalent diphtheria toxoid, tetanus toxoid, 3-component acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine

BACKGROUND: In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron(R)) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, polio, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany. METHODS: Healthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6--8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study. RESULTS: In the intent-to-treat population, paracetamol reduced the incidence of fever >=38[degree sign]C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: -19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39[degree sign]C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39[degree sign]C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported. CONCLUSIONS: Paracetamol effectively prevented fever and other reactions, mainly during the infant series. However, as events were generally mild and of no concern in either group our data support current recommendations to administer paracetamol to treat symptoms only and not for routine prophylaxis.Trial registration: NCT00294294

Gleichberechtigte Teilhabe im Sportunterricht – eine videobasierte Lehrveranstaltung zu heterogenen Schülervoraussetzungen

Im Sportunterricht geht es nicht nur um die Entwicklung körperlich-motorischer Fähigkeiten, sondern auch um die Förderung kognitiver und sozialer Kompetenzen. Auf Seiten der Sportlehrkraft erfordert dies unterschiedliche, parallel ablaufende Aufmerksamkeiten im Unterricht. Vor diesem Hintergrund wird im Beitrag ein Fachdidaktik-Seminar im Master of Education vorgestellt, in dem die Professionelle Unterrichtswahrnehmung in inklusiven Settings anhand von videographierten Spielen im Sportunterricht in der Sekundarstufe I gefördert wird. Im Vordergrund steht dabei die gleichberechtigte Teilhabe aller Schüler*innen, die in Teilnahme, Teilgabe und Teilsein differenziert wird (vgl. Pfitzner, 2017). Professionell wahrzunehmen bedeutet in diesem Kontext, die Aufmerksamkeit unter einem spezifischen Wahrnehmungsfokus zu steuern und die in den Blick genommenen Ereignisse unter Zuhilfenahme theoretischen Wissens zu deuten und zu verknüpfen (vgl. Sherin & van Es, 2009). Im Beitrag wird zunächst das zugrundeliegende Wahrnehmungskonzept für die gleichberechtigte Teilhabe vorgestellt und in Bezug zum inklusiven Sportunterricht gesetzt. Bevor die methodischen Entscheidungen für das Seminarkonzept dargestellt und begründet werden, erfolgt eine Verortung des Seminars im Modul „Sportdidaktik“ an der Universität Münster. Im Folgenden wird der Aufbau des Seminars beschrieben; dabei wird ein Überblick über die Ziele und Inhalte der einzelnen Seminarsitzungen gegeben. Ausgewählte Ergebnisse der Seminarevaluation und ein Ausblick beschließen den Beitrag

Detection of Large Vessel Occlusions using Deep Learning by Deforming Vessel Tree Segmentations

Computed Tomography Angiography is a key modality providing insights into the cerebrovascular vessel tree that are crucial for the diagnosis and treatment of ischemic strokes, in particular in cases of large vessel occlusions (LVO). Thus, the clinical workflow greatly benefits from an automated detection of patients suffering from LVOs. This work uses convolutional neural networks for case-level classification trained with elastic deformation of the vessel tree segmentation masks to artificially augment training data. Using only masks as the input to our model uniquely allows us to apply such deformations much more aggressively than one could with conventional image volumes while retaining sample realism. The neural network classifies the presence of an LVO and the affected hemisphere. In a 5-fold cross validated ablation study, we demonstrate that the use of the suggested augmentation enables us to train robust models even from few data sets. Training the EfficientNetB1 architecture on 100 data sets, the proposed augmentation scheme was able to raise the ROC AUC to 0.85 from a baseline value of 0.56 using no augmentation. The best performance was achieved using a 3D-DenseNet yielding an AUC of 0.87. The augmentation had positive impact in classification of the affected hemisphere as well, where the 3D-DenseNet reached an AUC of 0.93 on both sides.Comment: 7 pages. Accepted at BVM-Workshop 2022, Springe

Functional characterization of the KNOLLE-interacting t-SNARE AtSNAP33 and its role in plant cytokinesis

Cytokinesis requires membrane fusion during cleavage-furrow ingression in animals and cell plate formation in plants. In Arabidopsis, the Sec1 homologue KEULE (KEU) and the cytokinesis-specific syntaxin KNOLLE (KN) cooperate to promote vesicle fusion in the cell division plane. Here, we characterize AtSNAP33, an Arabidopsis homologue of the t-SNARE SNAP25, that was identified as a KN interactor in a yeast two-hybrid screen. AtSNAP33 is a ubiquitously expressed membrane-associated protein that accumulated at the plasma membrane and during cell division colocalized with KN at the forming cell plate. A T-DNA insertion in the AtSNAP33 gene caused loss of AtSNAP33 function, resulting in a lethal dwarf phenotype. atsnap33 plantlets gradually developed large necrotic lesions on cotyledons and rosette leaves, resembling pathogen-induced cellular responses, and eventually died before flowering. In addition, mutant seedlings displayed cytokinetic defects, and atsnap33 in combination with the cytokinesis mutant keu was embryo lethal. Analysis of the Arabidopsis genome revealed two further SNAP25-like proteins that also interacted with KN in the yeast two-hybrid assay. Our results suggest that AtSNAP33, the first SNAP25 homologue characterized in plants, is involved in diverse membrane fusion processes, including cell plate formation, and that AtSNAP33 function in cytokinesis may be replaced partially by other SNAP25 homologues

High lipid order of Arabidopsis cell‐plate membranes mediated by sterol and DYNAMIN‐RELATED PROTEIN1A function

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/1/tpj12674.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/2/tpj12674-sup-0002-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/3/tpj12674-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/4/tpj12674-sup-0003-FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/109568/5/tpj12674-sup-0004-FigS4.pd

Endocytosis restricts Arabidopsis KNOLLE syntaxin to the cell division plane during late cytokinesis

Cytokinesis represents the final stage of eukaryotic cell division during which the cytoplasm becomes partitioned between daughter cells. The process differs to some extent between animal and plant cells, but proteins of the syntaxin family mediate membrane fusion in the plane of cell division in diverse organisms. How syntaxin localization is kept in check remains elusive. Here, we report that localization of the Arabidopsis KNOLLE syntaxin in the plane of cell division is maintained by sterol-dependent endocytosis involving a clathrin- and DYNAMIN-RELATED PROTEIN1A-dependent mechanism. On genetic or pharmacological interference with endocytosis, KNOLLE mis-localizes to lateral plasma membranes after cell-plate fusion. Fluorescence-loss-in-photo-bleaching and fluorescence-recovery-after-photo-bleaching experiments reveal lateral diffusion of GFP-KNOLLE from the plane of division to lateral membranes. In an endocytosis-defective sterol biosynthesis mutant displaying lateral KNOLLE diffusion, KNOLLE secretory trafficking remains unaffected. Thus, restriction of lateral diffusion by endocytosis may serve to maintain specificity of syntaxin localization during late cytokinesis

Wahrheit – Geschwindigkeit – Pluralität

Neue Techniken zur Informationsübermittlung befördern den Informationsaustausch. Das ist eine für das 20. und 21. Jahrhundert ganz selbstverständliche Feststellung. Genauso selbstverständlich gilt sie aber auch für das 16. Jahrhundert und die Frühe Neuzeit insgesamt. Ein allseits bekanntes Beispiel dafür ist die Verbesserung der Techniken des Buchdrucks durch die Verwendung beweglicher Lettern. Dies führte dazu, dass neue Medien entstanden und sich dauerhaft etablierten, wie z.B. die Flugschrift und die „Neue Zeitung“. Andere bereits bekannte Genera wie Lieder und Predigten erhielten durch die veränderte Kommunikationssituation eine neue Bedeutung in den Auseinandersetzungen der Zeit. Daraus ergaben sich vielfältige Chancen und Heraus­forderungen, denn die Nutzung dieser neuen Medien wie die Transformation bestehender Medienformate und deren flächendeckende Verwendung setzte politische, soziale, juristische und religiöse Veränderungsprozesse in Gang bzw. beförderte sie.Die Beiträge des Sammelbandes möchten diese neuen Kommunikationsformen und -methoden ebenso wie die Veränderungsprozesse für das 16. Jahrhundert ausleuchten. Dies geschieht, indem Wandlungs- und Transformationsprozesse durch die Nutzung bekannter sowie die Schaffung neuer Medienformate, der Umgang mit Meinungsvielfalt und der damit einhergehenden Pluralität an Deutungen des Zeitgeschehens sowie die Entstehung einer neuen Streitkultur und neue Ordnungsversuche analysiert werden

A time-resolved proteomic and prognostic map of COVID-19.

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease